Aggregation by peptide conjugation rescues poor immunogenicity of the HA stem
AuthorJiang, W; Pilkington, EH; Kelly, HG; Tan, H-X; Juno, JA; Wheatley, AK; Kent, SJ
Source TitlePLoS One
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sKent, Stephen; Wheatley, Adam; Juno, Jennifer; Pilkington, Emily; Tan, Hyon Xhi
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsJiang, W., Pilkington, E. H., Kelly, H. G., Tan, H. -X., Juno, J. A., Wheatley, A. K. & Kent, S. J. (2020). Aggregation by peptide conjugation rescues poor immunogenicity of the HA stem. PLOS ONE, 15 (11), https://doi.org/10.1371/journal.pone.0241649.
Access StatusOpen Access
Influenza virus infection is a global public health threat. Current seasonal influenza vaccines are efficacious only when vaccine strains are matched with circulating strains. There is a critical need for developing "universal" vaccines that protect against all influenza viruses. HA stem is a promising target for developing broad-spectrum influenza vaccines due to its relatively conserved feature. However, HA stem is weakly immunogenic when administered alone in a soluble form. Several approaches have been employed to improve the immunogenicity of HA stem, including conjugation of HA stem with a highly immunogenic carrier protein or displaying HA stem on a nanoparticle scaffold. Converting a weakly immunologic protein into a multimer through aggregation can significantly enhance its immunogenicity, with some multimeric protein aggregates previously shown to be more immunogenic than their soluble counterparts in animal models. Here, we show that a chemically coupling a peptide derived from the head domain of PR8 HA (P35) with the poorly immunogenic HA stem protein results in aggregation of the HA stem which significantly increases stem-specific B cell responses following vaccination. Importantly, vaccination with this conjugate in the absence of adjuvant still induced robust B cell responses against stem in vivo. Improving HA stem immunogenicity by aggregation provides an alternative avenue to conjugation with exotic carrier proteins or nanoparticle formulation.
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